Last update 01 Nov 2024

Angiostatin

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction-

Drugs associated with Angiostatin

OXB-202

Target

Angiostatin

Mechanism

Angiostatin inhibitors

Active Org.

Oxford Biomedica Plc

Originator Org.

Oxford Biomedica Plc

Active Indication

Keratoplasty rejection

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Angiostatin

100 Translational Medicine associated with Angiostatin

0 Patents (Medical) associated with Angiostatin

574

Literatures (Medical) associated with Angiostatin

01 Sep 2024·Reproductive Sciences

The Essential Role of PGF2α/PTGFR in Molding Endometrial Breakdown and Vascular Dynamics, Regulated by HIF-1α in a Mouse Menstrual-like Model

Article

Author: Lu, Wenhong ; Long, Zeyi ; Guo, Shige ; Lu, Cong ; Chen, Xihua ; Zhou, Fang ; Zhuang, Taifeng ; Zhang, Xin ; Xu, Xiangbo ; Wang, Siyu ; Wang, Shufang ; Wu, Jiangxu ; He, Bin

In women of childbearing age, extensive decidualization, shedding and remodeling of the endometrium during the menstrual cycle are fundamental for successful pregnancy. The role of prostaglandins (PGs) in menstruation has long been proposed in humans, and the rate-limiting enzyme cyclooxygenase was shown to play a key role in endometrial breakdown and shedding in a mouse menstrual-like model in our previous study. However, the specific types of PGs involved and their respective roles remain unclear. Therefore, our objective was to investigate the mechanism through which PGs regulate endometrial disintegration. In this study, the microscopy was observed by HE; the protein levels of prostaglandins E1 (PGE1), prostaglandins E2 (PGE2), prostaglandin F2α (PGF2α) and Prostaglandin I2 (PGI2) were detected by ELISA; the mRNA level of Pfgfr2, Vascular Endothelial Growth Factor(Vegf), Angiostatin and Hypoxia inducible factor-1α (Hif1α) were examined by real-time PCR; PTGFR Receptor (PTGFR), VEGF, Angiostatin and HIF-1α protein levels were investigated by western blotting; the locations of protein were observed by Immunohistochemistry; HIF-1α binding PTGFR promoter was detected by Chromatin Immunoprecipitation (ChIP) and real-time PCR. We found that the concentrations of PGE1, PGE2, and PGF2α all increased significantly during this process. Furthermore, Ptgfr mRNA increased soon after Progesterone (P4) withdrawal, and PTGFR protein levels increased significantly during abundant endometrial breakdown and shedding processes. PTGFR inhibitors AL8810 significantly suppressed endometrial breakdown and shedding, promoted Angiostatin expression, and reduced VEGF-A expressions and vascular permeability. And HIF-1α and PTGFR were mainly located in the luminal/gland epithelium, vascular endothelium, and pre-decidual zone. Interestingly, HIF-1α directly bound to Ptgfr promoter. Moreover, a HIF-1α inhibitor 2-methoxyestradiol (2ME) significantly reduced PTGFR expression and suppressed endometrial breakdown which was in accord with PTGFR inhibitor's effect. Similar changes occurred in human stromal cells relevant to menstruation in vitro. Our study provides evidence that PGF2α/PTGFR plays a vital role in endometrial breakdown via vascular changes that are regulated by HIF-1α during menstruation.

15 Aug 2024·Heliyon

Anti-angiogenic activity of a novel angiostatin-like plasminogen fragment produced by a bacterial metalloproteinase.

Article

Author: Nishimura, Naoko ; Wang, Taolin ; Suzuki, Eriko ; Yamamoto, Tetsuro ; Hasumi, Keiji ; Shimizu, Kosuke

Tumor growth depends on angiogenesis, a process by which new blood vessel are formed from pre-existing normal blood vessels. Proteolytic fragments of plasminogen, containing varying numbers of plasminogen kringle domains, collectively known as angiostatin, are a naturally occurring inhibitor of angiogenesis and inhibit tumor growth. We have developed an "affinity-capture reactor" that enables a single-step method for the production/purification of an angiostatin-like plasminogen fragment from human plasma using an immobilized bacterial metalloproteinase. The resulting fragment, named BL-angiostatin, contains one or two glycosyl chains and the N-terminal PAN module, which are not present in canonical angiostatins tested for cancer treatment. BL-angiostatin inhibited angiogenesis in vitro at 20 nM and the growth of both allograft and human xenograft tumors as well as lung metastasis of primary tumors mice at 0.3-10 mg kg^-1. Derivatives of BL angiostatin lacking the PAN module or the terminal sialic acids in the glycosyl chains showed reduced anti-angiogenic activity in vivo, suggesting a role for these functions in activity, possibly via conferring a pharmacokinetic advantage to BL angiostatin compared to recombinant angiostatin lacking both features. These results highlight the potential of BL-angiostatin for therapeutic applications.

01 Aug 2024·JTCVS Open

Intramyocardial injection of hypoxia-conditioned extracellular vesicles increases myocardial perfusion in a swine model of chronic coronary disease

Article

Author: Sellke, Frank W. ; Abid, M. Ruhul ; Broadwin, Mark ; Sellke, Frank W ; Malhotra, Akshay ; Stone, Christopher ; Sabe, Sharif A ; Kanuparthy, Meghamsh ; Xu, Cynthia ; Harris, Dwight D ; Sabe, Sharif A. ; Abid, M Ruhul ; Harris, Dwight D.

ObjectiveCoronary artery disease remains a leading cause of morbidity and mortality worldwide. Patients with advanced coronary artery disease who are not eligible for endovascular or surgical revascularization have limited options. Extracellular vesicles have shown potential to improve myocardial function in preclinical models. Extracellular vesicles can be conditioned to modify their components. Hypoxia-conditioned extracellular vesicles have demonstrated the ability to reduce infarct size and apoptosis in small animals. Our objective is to assess the potential benefits of hypoxia-conditioned extracellular vesicles in a large animal model of coronary artery disease.MethodsCoronary artery disease was induced in 14 Yorkshire swine by ameroid constriction of the left circumflex coronary artery. Two weeks postsurgery, swine underwent a repeat left thoracotomy for injections of hypoxia-conditioned extracellular vesicles (n = 7) or saline (control, n = 7). Five weeks later, all animals underwent terminal harvest for perfusion measurements and myocardial sectioning.ResultsMyocardial perfusion analysis demonstrated a trend toward increase at rest and a significant increase during rapid pacing (P = .09, P < .001). There were significant increases in activated phosphorylated endothelial nitric oxide synthase, endothelial nitric oxide synthase, phosphatidylinositol 3-kinase, phosphorylated protein kinase B, and the phosphorylated protein kinase B/protein kinase B ratio in the hypoxia-conditioned extracellular vesicles group compared with the control group (all P < .05). Additionally, there was a significant decrease in the antiangiogenic proteins collagen 18 and angiostatin (P = .01, P = .01) in the hypoxia-conditioned extracellular vesicles group.ConclusionsIntramyocardial injection of hypoxia-conditioned extracellular vesicles results in increased myocardial perfusion without a corresponding change in vessel density. Therefore, this improvement in perfusion is possibly due to changes in nitric oxide signaling. Hypoxia-conditioned extracellular vesicles represent a potential therapeutic strategy to increase myocardial perfusion in patients with advanced coronary artery disease.

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Angiostatin

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